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Article Open Access

Hepatitis B envelope antigen increases Tregs by converting CD4+CD25‑ T cells into CD4+CD25+Foxp3+ Tregs

  • Authors:
    • Rui Tang
    • Zhigang Lei
    • Xinpeng Wang
    • Qianqian Qi
    • Jingjing He
    • Dan Liu
    • Xiaoxian Wang
    • Xiaojun Chen
    • Jifeng Zhu
    • Yalin Li
    • Sha Zhou
    • Chuan Su
  • View Affiliations / Copyright

    Affiliations: State Key Laboratory of Reproductive Medicine, Department of Pathogen Biology and Immunology, Jiangsu Key Laboratory of Pathogen Biology, Center for Global Health, Nanjing Medical University, Nanjing, Jiangsu 211166, P.R. China
    Copyright: © Tang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 3679-3686
    |
    Published online on: August 6, 2020
       https://doi.org/10.3892/etm.2020.9107
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Abstract

Hepatitis B virus (HBV) can establish a lifelong chronic infection in humans, leading to liver cirrhosis, liver failure and hepatocellular carcinoma. Patients with chronic hepatitis B (CHB) exhibit a weak virus‑specific immune response. Regulatory T cells (Tregs) play a key role in regulating the immune response in patients with CHB. Patients with hepatitis B envelope antigen (HBeAg)‑positive CHB harbored a higher percentage of Tregs in their peripheral blood than those with HBeAg‑negative CHB. However, whether and how HBeAg manipulates the host immune system to increase the population of Tregs remains to be elucidated. The present manuscript describes a preliminary immunological study of HBeAg in a mouse model. Multiple potential CD4+ T cell epitopes in HBeAg were identified using Immune Epitope Database consensus binding prediction. It was demonstrated that HBeAg treatment increased the numbers of Tregs in mouse spleens in vitro and in vivo. Furthermore, it was indicated that the HBeAg‑mediated increase in Tregs occurred through the conversion of CD4+CD25‑ T cells into CD4+CD25+Foxp3+ Tregs. Additionally, in vitro study illustrated that HBeAg stimulated murine spleen cells to produce increased transforming growth factor‑β, which is required to enable HBeAg to convert T cells into Tregs. The results of the present study may provide further evidence of the effect of HBeAg on Tregs and aid in the development of novel HBeAg‑based immunotherapy for CHB.
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1 

Seto WK, Lo YR, Pawlotsky JM and Yuen MF: Chronic hepatitis B virus infection. Lancet. 392:2313–2324. 2018.PubMed/NCBI View Article : Google Scholar

2 

Yuen MF, Chen DS, Dusheiko GM, Janssen HLA, Lau DTY, Locarnini SA, Peters MG and Lai CL: Hepatitis B virus infection. Nat Rev Dis Primers. 4(18035)2018.PubMed/NCBI View Article : Google Scholar

3 

Maini MK and Pallett LJ: Defective T-cell immunity in hepatitis B virus infection: Why therapeutic vaccination needs a helping hand. Lancet Gastroenterol Hepatol. 3:192–202. 2018.PubMed/NCBI View Article : Google Scholar

4 

Park JJ, Wong DK, Wahed AS, Lee WM, Feld JJ, Terrault N, Khalili M, Sterling RK, Kowdley KV, et al: Hepatitis B virus--specific and global T-cell dysfunction in chronic hepatitis B. Gastroenterology. 150:684–695.e5. 2016.PubMed/NCBI View Article : Google Scholar

5 

Bertoletti A and Naoumov NV: Translation of immunological knowledge into better treatments of chronic hepatitis B. J Hepatol. 39:115–124. 2003.PubMed/NCBI View Article : Google Scholar

6 

Bertoletti A and Ferrari C: Innate and adaptive immune responses in chronic hepatitis B virus infections: Towards restoration of immune control of viral infection. Gut. 61:1754–1764. 2012.PubMed/NCBI View Article : Google Scholar

7 

Bertoletti A and Ferrari C: Kinetics of the immune response during HBV and HCV infection. Hepatology. 38:4–13. 2003.PubMed/NCBI View Article : Google Scholar

8 

Chang C, Enders G, Sprengel R, Peters N, Varmus HE and Ganem D: Expression of the precore region of an avian hepatitis B virus is not required for viral replication. J Virol. 61:3322–3325. 1987.PubMed/NCBI View Article : Google Scholar

9 

Chen HS, Kew MC, Hornbuckle WE, Tennant BC, Cote PJ, Gerin JL, Purcell RH and Miller RH: The precore gene of the woodchuck hepatitis virus genome is not essential for viral replication in the natural host. J Virol. 66:5682–5684. 1992.PubMed/NCBI View Article : Google Scholar

10 

Schlicht HJ, Salfeld J and Schaller H: The duck hepatitis B virus pre-C region encodes a signal sequence which is essential for synthesis and secretion of processed core proteins but not for virus formation. J Virol. 61:3701–3709. 1987.PubMed/NCBI View Article : Google Scholar

11 

Boni C, Laccabue D, Lampertico P, Giuberti T, Viganò M, Schivazappa S, Alfieri A, Pesci M, Gaeta GB, et al: Restored function of HBV-specific T cells after long-term effective therapy with nucleos(t)ide analogues. Gastroenterology. 143:963–973.e9. 2012.PubMed/NCBI View Article : Google Scholar

12 

Chen M, Sällberg M, Hughes J, Jones J, Guidotti LG, Chisari FV, Billaud JN and Milich DR: Immune tolerance split between hepatitis B virus precore and core proteins. J Virol. 79:3016–3027. 2005.PubMed/NCBI View Article : Google Scholar

13 

Milich D and Liang TJ: Exploring the biological basis of hepatitis B e antigen in hepatitis B virus infection. Hepatology. 38:1075–1086. 2003.PubMed/NCBI View Article : Google Scholar

14 

Manigold T and Racanelli V: T-cell regulation by CD4 regulatory T cells during hepatitis B and C virus infections: Facts and controversies. Lancet Infect Dis. 7:804–813. 2007.PubMed/NCBI View Article : Google Scholar

15 

Stoop JN, van der Molen RG, Baan CC, van der Laan LJ, Kuipers EJ, Kusters JG and Janssen HL: Regulatory T cells contribute to the impaired immune response in patients with chronic hepatitis B virus infection. Hepatology. 41:771–778. 2005.PubMed/NCBI View Article : Google Scholar

16 

Aalaei-Andabili SH and Alavian SM: Regulatory T cells are the most important determinant factor of hepatitis B infection prognosis: A systematic review and meta-analysis. Vaccine. 30:5595–5602. 2012.PubMed/NCBI View Article : Google Scholar

17 

Lin CY, Tsai MC, Huang CT, Hsu CW, Tseng SC, Tsai IF, Chen YC, Yeh CT, Sheen IS and Chien RN: Liver injury is associated with enhanced regulatory T-cell activity in patients with chronic hepatitis B. J Viral Hepat. 14:503–511. 2007.PubMed/NCBI View Article : Google Scholar

18 

Stoop JN, van der Molen RG, Kuipers EJ, Kusters JG and Janssen HL: Inhibition of viral replication reduces regulatory T cells and enhances the antiviral immune response in chronic hepatitis B. Virology. 361:141–148. 2007.PubMed/NCBI View Article : Google Scholar

19 

El-Badawy O, Sayed D, Badary MS, Abd-Alrahman ME, El-Feky MA and Thabit AG: Relations of regulatory T cells with hepatitis markers in chronic hepatitis B virus infection. Hum Immunol. 73:335–341. 2012.PubMed/NCBI View Article : Google Scholar

20 

Peng G, Li S, Wu W, Sun Z, Chen Y and Chen Z: Circulating CD4+ CD25+ regulatory T cells correlate with chronic hepatitis B infection. Immunology. 123:57–65. 2008.PubMed/NCBI View Article : Google Scholar

21 

Chen W, Jin W, Hardegen N, Lei KJ, Li L, Marinos N, McGrady G and Wahl SM: Conversion of peripheral CD4+CD25- naive T cells to CD4+CD25+ regulatory T cells by TGF-beta induction of transcription factor Foxp3. J Exp Med. 198:1875–1886. 2003.PubMed/NCBI View Article : Google Scholar

22 

Peng Y, Laouar Y, Li MO, Green EA and Flavell RA: TGF-beta regulates in vivo expansion of Foxp3-expressing CD4+CD25+ regulatory T cells responsible for protection against diabetes. Proc Natl Acad Sci USA. 101:4572–4577. 2004.PubMed/NCBI View Article : Google Scholar

23 

Maruyama T, Iino S, Koike K, Yasuda K and Milich DR: Serology of acute exacerbation in chronic hepatitis B virus infection. Gastroenterology. 105:1141–1151. 1993.PubMed/NCBI View Article : Google Scholar

24 

Masopust D, Sivula CP and Jameson SC: Of mice, dirty mice, and men: Using mice To understand human immunology. J Immunol. 199:383–388. 2017.PubMed/NCBI View Article : Google Scholar

25 

Turner MS, Kane LP and Morel PA: Dominant role of antigen dose in CD4+Foxp3+ regulatory T cell induction and expansion. J Immunol. 183:4895–4903. 2009.PubMed/NCBI View Article : Google Scholar

26 

Shevach EM: From vanilla to 28 flavors: Multiple varieties of T regulatory cells. Immunity. 25:195–201. 2006.PubMed/NCBI View Article : Google Scholar

27 

Kang J, Huddleston SJ, Fraser JM and Khoruts A: De novo induction of antigen-specific CD4+CD25+Foxp3+ regulatory T cells in vivo following systemic antigen administration accompanied by blockade of mTOR. J Leukoc Biol. 83:1230–1239. 2008.PubMed/NCBI View Article : Google Scholar

28 

Gottschalk RA, Corse E and Allison JP: TCR ligand density and affinity determine peripheral induction of Foxp3 in vivo. J Exp Med. 207:1701–1711. 2010.PubMed/NCBI View Article : Google Scholar

29 

Li MO and Rudensky AY: T cell receptor signalling in the control of regulatory T cell differentiation and function. Nat Rev Immunol. 16:220–233. 2016.PubMed/NCBI View Article : Google Scholar

30 

Moon JJ, Chu HH, Pepper M, McSorley SJ, Jameson SC, Kedl RM and Jenkins MK: Naive CD4(+) T cell frequency varies for different epitopes and predicts repertoire diversity and response magnitude. Immunity. 27:203–213. 2007.PubMed/NCBI View Article : Google Scholar

31 

Josefowicz SZ, Lu LF and Rudensky AY: Regulatory T cells: Mechanisms of differentiation and function. Annu Rev Immunol. 30:531–564. 2012.PubMed/NCBI View Article : Google Scholar

32 

Khorramdelazad H, Hassanshahi G, Nasiri Ahmadabadi B and Kazemi Arababadi M: High serum levels of TGF-β in Iranians with chronic HBV infection. Hepat Mon. 12(e7581)2012.PubMed/NCBI View Article : Google Scholar

33 

Li H, Zhai N, Wang Z, Song H, Yang Y, Cui A, Li T, Wang G, Niu J, Crispe IN, et al: Regulatory NK cells mediated between immunosuppressive monocytes and dysfunctional T cells in chronic HBV infection. Gut. 67:2035–2044. 2018.PubMed/NCBI View Article : Google Scholar

34 

Tsai KN, Kuo CF and Ou JJ: Mechanisms of hepatitis B virus persistence. Trends Microbiol. 26:33–42. 2018.PubMed/NCBI View Article : Google Scholar

35 

Yang F, Yu X, Zhou C, Mao R, Zhu M, Zhu H, Ma Z, Mitra B, Zhao G, et al: Hepatitis B e antigen induces the expansion of monocytic myeloid-derived suppressor cells to dampen T-cell function in chronic hepatitis B virus infection. PLoS Pathog. 15(e1007690)2019.PubMed/NCBI View Article : Google Scholar

36 

Ciupe SM: Modeling the dynamics of hepatitis B infection, immunity, and drug therapy. Immunol Rev. 285:38–54. 2018.PubMed/NCBI View Article : Google Scholar

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Copy and paste a formatted citation
Spandidos Publications style
Tang R, Lei Z, Wang X, Qi Q, He J, Liu D, Wang X, Chen X, Zhu J, Li Y, Li Y, et al: Hepatitis B envelope antigen increases Tregs by converting CD4+CD25‑ T cells into CD4+CD25+Foxp3+ Tregs. Exp Ther Med 20: 3679-3686, 2020.
APA
Tang, R., Lei, Z., Wang, X., Qi, Q., He, J., Liu, D. ... Su, C. (2020). Hepatitis B envelope antigen increases Tregs by converting CD4+CD25‑ T cells into CD4+CD25+Foxp3+ Tregs. Experimental and Therapeutic Medicine, 20, 3679-3686. https://doi.org/10.3892/etm.2020.9107
MLA
Tang, R., Lei, Z., Wang, X., Qi, Q., He, J., Liu, D., Wang, X., Chen, X., Zhu, J., Li, Y., Zhou, S., Su, C."Hepatitis B envelope antigen increases Tregs by converting CD4+CD25‑ T cells into CD4+CD25+Foxp3+ Tregs". Experimental and Therapeutic Medicine 20.4 (2020): 3679-3686.
Chicago
Tang, R., Lei, Z., Wang, X., Qi, Q., He, J., Liu, D., Wang, X., Chen, X., Zhu, J., Li, Y., Zhou, S., Su, C."Hepatitis B envelope antigen increases Tregs by converting CD4+CD25‑ T cells into CD4+CD25+Foxp3+ Tregs". Experimental and Therapeutic Medicine 20, no. 4 (2020): 3679-3686. https://doi.org/10.3892/etm.2020.9107
Copy and paste a formatted citation
x
Spandidos Publications style
Tang R, Lei Z, Wang X, Qi Q, He J, Liu D, Wang X, Chen X, Zhu J, Li Y, Li Y, et al: Hepatitis B envelope antigen increases Tregs by converting CD4+CD25‑ T cells into CD4+CD25+Foxp3+ Tregs. Exp Ther Med 20: 3679-3686, 2020.
APA
Tang, R., Lei, Z., Wang, X., Qi, Q., He, J., Liu, D. ... Su, C. (2020). Hepatitis B envelope antigen increases Tregs by converting CD4+CD25‑ T cells into CD4+CD25+Foxp3+ Tregs. Experimental and Therapeutic Medicine, 20, 3679-3686. https://doi.org/10.3892/etm.2020.9107
MLA
Tang, R., Lei, Z., Wang, X., Qi, Q., He, J., Liu, D., Wang, X., Chen, X., Zhu, J., Li, Y., Zhou, S., Su, C."Hepatitis B envelope antigen increases Tregs by converting CD4+CD25‑ T cells into CD4+CD25+Foxp3+ Tregs". Experimental and Therapeutic Medicine 20.4 (2020): 3679-3686.
Chicago
Tang, R., Lei, Z., Wang, X., Qi, Q., He, J., Liu, D., Wang, X., Chen, X., Zhu, J., Li, Y., Zhou, S., Su, C."Hepatitis B envelope antigen increases Tregs by converting CD4+CD25‑ T cells into CD4+CD25+Foxp3+ Tregs". Experimental and Therapeutic Medicine 20, no. 4 (2020): 3679-3686. https://doi.org/10.3892/etm.2020.9107
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